Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, China.
Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, China.
J Cell Mol Med. 2022 Feb;26(3):593-600. doi: 10.1111/jcmm.16236. Epub 2021 Jan 19.
The recovery of blood supply after a period of myocardial ischaemia does not restore the heart function and instead results in a serious dysfunction called myocardial ischaemia-reperfusion injury (IRI), which involves several complex pathophysiological processes. Mitochondria have a wide range of functions in maintaining the cellular energy supply, cell signalling and programmed cell death. When mitochondrial function is insufficient or disordered, it may have adverse effects on myocardial ischaemia-reperfusion and therefore mitochondrial dysfunction caused by oxidative stress a core molecular mechanism of IRI. Peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) is an important antioxidant molecule found in mitochondria. However, its role in IRI has not yet been systematically summarized. In this review, we speculate the role of PGC-1α as a key regulator of mitonuclear communication, which may interacts with nuclear factor, erythroid 2 like -1 and -2 (NRF-1/2) to inhibit mitochondrial oxidative stress, promote the clearance of damaged mitochondria, enhance mitochondrial biogenesis, and reduce the burden of IRI.
在一段心肌缺血期后恢复血液供应并不会恢复心脏功能,反而会导致一种称为心肌缺血再灌注损伤 (IRI) 的严重功能障碍,其中涉及几个复杂的病理生理过程。线粒体在维持细胞能量供应、细胞信号转导和程序性细胞死亡方面具有广泛的功能。当线粒体功能不足或紊乱时,可能会对心肌缺血再灌注产生不利影响,因此氧化应激引起的线粒体功能障碍是 IRI 的核心分子机制。过氧化物酶体增殖物激活受体 γ 共激活因子 1α (PGC-1α) 是在线粒体中发现的一种重要抗氧化分子。然而,其在 IRI 中的作用尚未得到系统总结。在这篇综述中,我们推测 PGC-1α 作为线粒体与核之间通讯的关键调节剂的作用,它可能与核因子、红系 2 样因子 1 和 2 (NRF-1/2) 相互作用,抑制线粒体氧化应激,促进受损线粒体的清除,增强线粒体生物发生,并减轻 IRI 的负担。